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ACE2 inhibits proliferation of smooth muscle cell through AT1R and its downstream signaling pathway

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Abstract

To investigate the effect of the angiotensin converting enzyme 2 (ACE2) on AT1R expression, ERK1/2 and STAT3 protein phosphorylation in rat vascular smooth muscle cells (VSMCs) was studied. VSMCs were transfected with a lentiviral vector including the ACE2 gene and with siRNA to regulate the level of ACE2 in VSMCs. The levels of mRNA and proteins of ACE2, AT1R, ERK1/2, p-ERK1/2, STAT3, and p-STAT3 in VSMCs were examined using real-time PCR and western blot. The proliferation of VSMCs was observed by CCK-8 assay and BrdU measurement. Upregulation of ACE2 inhibited the growth of cells elicited by angiotensin II (Ang II). ACE2 significantly suppressed the level of the AT1 receptor (AT1R) protein induced by Ang II and phosphorylated the ERK1/2 and STAT3 proteins in the downstream signaling pathway. The transcriptional and translational levels of ACE2 were significantly lower in the si-ACE2 group than in the control group. The level of AT1R mRNA and protein, both with the phosphorylation expression of ERK1/2 and STAT3 protein in the si-ACE2 group and the Ang II group, were significantly enhanced than those in the control group. ACE2 significantly inhibited the growth of VSMCs. ACE2 inhibited the proliferation of VSMCs by suppressing AT1R and the downstream ERK1/2 and STAT3 signaling axes. Also, Ang II enhanced the level of AT1R and phosphorylated ERK1/2 and STAT3 by inhibiting the level of the ACE2 mRNA and protein.

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Acknowledgements

We sincerely thank all hospital staff for participating in and supporting this study.

Funding

This work was supported by grants from the Scientific Research Project of the Joint Funds for the Innovation of Science and Technology, Fujian Province (no. 2021Y9132), Professor Academic Development Fund of Fujian Medical University in China (no. JS14023), and Startup Fund for Scientific Research of Fujian Medical University (no. 2021QH1057).

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Authors and Affiliations

  1. Department of Cardiology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China

    Jingjing Gong & Zhuoqiang Lu

  2. National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China

    Jingjing Gong & Xueqing Jin

  3. Fujian Provincial Institute of Hypertension, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China

    Rongtong Li

  4. Department of Cadre Ward, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China

    Changsheng Xu & Xueqing Jin

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  1. Jingjing Gong
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  2. Zhuoqiang Lu
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  3. Rongtong Li
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  4. Changsheng Xu
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Correspondence to Xueqing Jin.

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The authors declare that there is no conflict of interest.

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Corresponding editor: Satyajit Rath

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Gong, J., Lu, Z., Li, R. et al. ACE2 inhibits proliferation of smooth muscle cell through AT1R and its downstream signaling pathway. J Biosci 48, 25 (2023). https://doi.org/10.1007/s12038-023-00339-1

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  • DOI: https://doi.org/10.1007/s12038-023-00339-1

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